Carrageenan injected into the rat pleural cavity induces after a short delay extravasation of serum protein, the appearance of neutrophil chemotactic factor (s) and, after 90 min, the infiltration of large numbers of neutrophils (80-140 times 10 to the 6th power cells/cavity). Pleural mast cells remained intact. Indomethacin given orally or intravenously aborted these reactions whether given before or after neutrophil infiltration started but, unlike other immunosuppressive drugs, did not affect production or release of white cells from bone marrow. The intrapleural injection of low molecular weight Dextrans (T10) provoked a similar reaction, but high molecular weight Dextrans (T70) promoted mast cell degranulation, extensive edema and little (less than 30 times 10 to the 6th power cells) neutrophil infiltration. Intermediate molecular weight Dextrans (T40 and T70) produced both reactions. The studies indicated that mast cell degranulation and neutrophil accumulation are distinct reactions, although both may occur simulatneously in some forms of exprimentally induced inflammation. Indomethacin inhibits specifically the neutrophil response.